Mutations And Metabolic Pathways Flashcards
Mutations and Mutagens
Mutation - a random and permanent change in the DNA base sequence.
Mutations can be spontaneous or induced. Spontaneous mutations occur during an error in DNA replication. They are rare, but increase as you age. Sometimes corrected by enzymes during the last stage of DNA replication. Induced mutations occur due to exposure to external factors called mutagens.
Point mutations are mutations that involve a single nucleotide (one base) or changes to one triplet. The three different types are substitution, insertion, and deletion.
Substitution Mutation
One base is replaced by another e.g. A is replaced by G. Substitution mutations can have different kinds of effects on the amino acid sequence and/or length of the polypeptide chain.
Same sense / silent mutation:
The base substitution could code for the same amino acid due to codon degeneracy. This would result in no change to sequence or length.
Missense mutation:
The base substitution could code for a different amino acid. This could replace an amino acid in the sequence or remove a STOP codon, making the polypeptide chain longer. This produces a non-functional protein.
Nonsense mutation:
The base substitution could code for one of the three STOP codons. This would shorten the length of the polypeptide chain by ending translation early. A non-functional protein is formed.
Degeneracy/Redundant Code
Codons that code for amino acids are degenerate or redundant. This is possible because there are 64 codon combinations but only 20 amino acids. Multiple codons code for the same amino acid. This is why same sense mutations don’t change the amino acid sequence (silent mutation). Codon degeneracy does not protect from all mutations.
Insertion Mutation
One or more bases are added to the sequence.
Deletion Mutation
One or more bases are removed from the sequence and not replaced.
Frameshift Mutations
Adding or removing a base changes all other DNA triplets after the point of the mutation. DNA triplets will get broken up and reordered.
All insertion and deletion mutations will lead to a reading frameshift as both these types of mutations change the total number of bases in the sequence and reorder the existing triplets. A frameshift results in a change to all the codons (and therefore amino acids) after the point of mutation, which will alter the final folding of the protein.
A frameshift can affect STOP codon by randomly generating a STOP codon in the middle of the mRNA strand or removing the STOP codon at the end of the mRNA strand, resulting in an endless polypeptide chain.
Impacts of Mutations
The largest impact on the amino acid sequence will occur through:
- Frameshift mutations which change all amino acids after the point of mutation.
- Nonsense mutations that shorten the overall length of the amino acid sequence.
- Missense mutations that remove a STOP codon and increase the overall length of the amino acid sequence.
- Any mutations closer to the start of the coding region of the gene (affects more DNA triplets).
A large impact on amino acid sequence will lead to the misfolding of the protein to be more likely, and so the final phenotype is likely to be altered.
Metabolism
This is the sum of all the physical and chemical reactions that are controlled by enzymes and take place within cells.
Types of Metabolism
Catabolism - the breakdown of molecules e.g. cellular respiration
Anabolism - the synthesis of molecules e.g. photosynthesis
Metabolic Pathways
Metabolic pathways are a series of enzyme-controlled reactions where the product of one reaction is the substrate for the next reaction. One gene codes for one enzyme in the pathway.
Enzymes control metabolic pathways by speeding up the series of reactions. They build up or break down chemicals, making the substrate for the next reaction in the series.
Disrupting Metabolic Pathways
The ability of each enzyme to transform the substrate into intermediates (or end products) is dependent on its shape, which is dependent on the gene that codes for that enzyme. Shape of protein (enzyme) determines its function.
If there is a mutation to the gene, a non-functional enzyme will be produced. This non-functional enzyme is unable to transform the substrate into intermediates (or end products) as the substrate cannot bind/fit properly to the non-functional enzymes active site.
This disrupts the metabolic pathway resulting in no end product being formed AND an accumulation of an initial (or intermediate substrate).
Effects of Disrupted Metabolic Pathways
The build up of an initial or intermediate substrate due to a mutation in one of the genes in the metabolic pathway can result in new phenotypes that are different to the phenotype that occurs when the pathway is correctly functioning.
Substrate build up can be toxic to the organism, resulting in metabolic disorders with new phenotypes.
Mutations’ Impact on Gene Expression
Mutations affect gene expression by interrupting metabolic pathways. A mutation results in a change in genotype, which impacts the amino acid sequence and final folding of a protein, leading to a change in phenotype.
A misfolded protein may have an incorrect active site, which will result in no enzyme-substrate complex being formed. This results in a change of phenotype due to the accumulation of intermediate or initial substrates, and therefore, a lack of an end product.
